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Nucleic Acids Research, 2003, Vol. 31, No. 11 2944-2951
© 2003 Oxford University Press

Specific interactions of distamycin with G-quadruplex DNA

Melanie J. Cocco, L. A. Hanakahi1, Michael D. Huber2 and Nancy Maizels2,3

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA, 1 Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA and 2 Department of Biochemistry and 3 Department of Immunology, University of Washington Medical School, Seattle, WA 98195-7650, USA

*To whom correspondence should be addressed. Tel: +1 203 432 9841; Fax: +1 203 432 5175; Email: cocco{at}csb.yale.edu

Distamycin binds the minor groove of duplex DNA at AT-rich regions and has been a valuable probe of protein interactions with double-stranded DNA. We find that distamycin can also inhibit protein interactions with G-quadruplex (G4) DNA, a stable four-stranded structure in which the repeating unit is a G-quartet. Using NMR, we show that distamycin binds specifically to G4 DNA, stacking on the terminal G-quartets and contacting the flanking bases. These results demonstrate the utility of distamycin as a probe of G4 DNA–protein interactions and show that there are (at least) two distinct modes of protein–G4 DNA recognition which can be distinguished by sensitivity to distamycin.


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